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Cited by 176

The DOI matches its Crossref record; 18 of the 18 references it cites were found in a registry or an index.

Mitochondrial Alterations in PINK1 Deficient Cells Are Influenced by Calcineurin-Dependent Dephosphorylation of Dynamin-Related Protein 1

Open access
Sandebring, Anna, Thomas, Kelly Jean, Beilina, Alexandra, van der Brug, Marcel, Cleland, Megan M., Ahmad, Rili, Miller, David W., Zambrano, Ibardo, Cowburn, Richard F., Behbahani, Homira, Cedazo-Mínguez, Angel, Cookson, Mark R.·2009·PLoS ONE

Abstract

PTEN-induced novel kinase 1 (PINK1) mutations are associated with autosomal recessive parkinsonism. Previous studies have shown that PINK1 influences both mitochondrial function and morphology although it is not clearly established which of these are primary events and which are secondary. Here, we describe a novel mechanism linking mitochondrial dysfunction and alterations in mitochondrial morphology related to PINK1. Cell lines were generated by stably transducing human dopaminergic M17 cells with lentiviral constructs that increased or knocked down PINK1. As in previous studies, PINK1 deficient cells have lower mitochondrial membrane potential and are more sensitive to the toxic effects of mitochondrial complex I inhibitors. We also show that wild-type PINK1, but not recessive mutant or kinase dead versions, protects against rotenone-induced mitochondrial fragmentation whereas PINK1 deficient cells show lower mitochondrial connectivity. Expression of dynamin-related protein 1 (Drp1) exaggerates PINK1 deficiency phenotypes and Drp1 RNAi rescues them. We also show that Drp1 is dephosphorylated in PINK1 deficient cells due to activation of the calcium-dependent phosphatase calcineurin. Accordingly, the calcineurin inhibitor FK506 blocks both Drp1 dephosphorylation and loss of mitochondrial integrity in PINK1 deficient cells but does not fully rescue mitochondrial membrane potential. We propose that alterations in mitochondrial connectivity in this system are secondary to functional effects on mitochondrial membrane potential.

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Metadata

Authors
Sandebring, A., Thomas, K. J., Beilina, A., van der Brug, M., Cleland, M. M., Ahmad, R., Miller, D. W., Zambrano, I., Cowburn, R. F., Behbahani, H., Cedazo-Mínguez, A., & Cookson, M. R.
Venue
PLoS ONE
Published
2009-05-27
Volume
4
Issue
5
Pages
e5701
ISSN
1932-6203 (ISSN-L)
OpenAlex
W2048621445
Cited by
176
References
18
FWCI
11.16
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: Mitochondrial Alterations in PINK1 Deficient Cells Are Influenced by Calcineurin-Dependent Dephosphorylation of Dynamin-Related Protein 1. https://app.cochat.ai/papers/10.1371/journal.pone.0005701
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Sandebring, A., Thomas, K. J., Beilina, A., van der Brug, M., Cleland, M. M., Ahmad, R., Miller, D. W., Zambrano, I., Cowburn, R. F., Behbahani, H., Cedazo-Mínguez, A., & Cookson, M. R. (2009). Mitochondrial Alterations in PINK1 Deficient Cells Are Influenced by Calcineurin-Dependent Dephosphorylation of Dynamin-Related Protein 1. PLoS ONE. https://doi.org/10.1371/journal.pone.0005701

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